Improvement in skin thickening in systemic sclerosis associated with improved survival

Objective. The natural history of changes in skin thickening in diffuse scl eroderma is quite variable, but the significance of these changes is not cl ear. Clinical trials are using changes in skin thickening as the primary ou tcome measure, and thus it would be helpful to determine the significance o f improvement in skin thickening. The purpose of the present study was to d etermine whether improvement in skin thickening over time was associated wi th improved survival. Methods. Patients with early (<3 years) diffuse scleroderma who had a basel ine evaluation and a repeat skin assessment (modified Rodnan skin score) pe rformed 2 years later (i.e., they had to live for 2 years) were identified from the prospective, observational Pittsburgh Scleroderma Databank. The pe rcentage of improvement and rate of change in the skin score during that ti me were determined. Patients with an improvement in their skin thickening o f >25% of their peak skin score and a rate of change of at least 5 units/ye ar were defined as the improved group; patients with increased skin thicken ing or no improvement were termed the no improvement group. Demographic and clinical features, organ system involvement, and survival rates were deter mined and the groups were compared. Regression and Cox regression analyses were used to determine what features were associated with improved skin thi ckness and survival. Results. Two hundred seventy-eight patients fulfilled the entry criteria, 6 3% in the improved group and 36% in the no improvement group. The groups we re similar in terms of clinical and demographic characteristics at the init ial visit. The improved group had an average improvement of 50% of their pe ak skin score at 2 years after the initial visit. Survival was significantl y better in the improved group compared with the unimproved group at 5 and 10 years, with rates of 90% and 80%, respectively, in the improved group an d 77% and 60%, respectively, in the no improvement group (P < 0.0001). Ther e were no significant differences in the occurrence of severe organ involve ment during the first 2 years to account for the later differences in survi val. The duration of the use of D-penicillamine was significantly associate d with improved skin thickness and improved survival. Conclusion. Among patients surviving the first few years of diffuse sclerod erma, striking improvement in skin thickening may occur in up to two-thirds . This improvement in skin thickening is associated with improved survival. Improvement in skin thickening may be useful as a surrogate for improvemen t in survival in clinical trials.